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Sacituzumab tirumotecan (sac-TMT), also known as SKB264 or MK-2870, is a TROP2-directed antibody-drug conjugate (ADC) consisting of a humanized monoclonal antibody targeting TROP2 conjugated to a belotecan-derivative topoisomerase I inhibitor payload via a hydrolytically cleavable linker. This combination therapy pairs sac-TMT with a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) to treat patients with EGFR-mutated non-small cell lung cancer (NSCLC), particularly those with brain metastases who have failed prior TKI therapy. The rationale for this combination is to leverage the targeted cytotoxic delivery of the ADC alongside the systemic and intracranial activity of the EGFR-TKI to overcome resistance and improve outcomes in advanced lung cancer.
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